Diagnostic, Therapeutic, and Theranostic Multifunctional Microneedles.

Microneedles (MNs) have maintained their popularity in therapeutic and diagnostic medical applications throughout the past decade. MNs are originally designed to gently puncture the stratum corneum layer of the skin and have lately evolved into intelligent devices with functions including bodily fluid extraction, biosensing, and drug administration. MNs offer limited invasiveness, ease of application, and minimal discomfort. Initially manufactured solely from metals, MNs are now available in polymer-based varieties. MNs can be used to create systems that deliver drugs and chemicals uniformly, collect bodily fluids, and are stimulus-sensitive. Although these advancements are favorable in terms of biocompatibility and production costs, they are insufficient for the therapeutic use of MNs. This is the first comprehensive review that discusses individual MN functions toward the evolution and development of smart and multifunctional MNs for a variety of novel and impactful future applications. The study examines fabrication techniques, application purposes, and experimental details of MN constructs that perform multiple functions concurrently, including sensing, drug-molecule release, sampling, and remote communication capabilities. It is highly likely that in the near future, MN-based smart devices will be a useful and important component of standard medical practice for different applications.

New cyclometalated iridium(III) complexes bearing substituted 2-(1H-benzimidazol-2-yl)quinoline: Synthesis, characterization, electrochemical and anticancer studies.

New iridium(III) compounds (C1-C3) bearing 2-(1H-benzimidazol-2-yl)quinoline ligands with different side groups (benzyl, 2,3,4,5,6-pentamethylbenzyl and 2,3,4,5,6-pentafluorobenzyl) were synthesized and characterized by using spectroscopic analyses. The effects of different side groups of iridium compounds on the photophysical and electrochemical properties have been investigated. The cytotoxicity and apoptosis of the compounds have been evaluated on breast cancer cell lines using various methods including MTT assay, flow cytometry, qRT-PCR, and colony formation. The cytotoxicity of C1, expressed as IC50 values, was found to be 11.76 µM for MDA-MB-231 and 5.35 µM for MCF-7 cells. For C3, the IC50 value was 16.22 µM for MDA-MB-231 and 8.85 µM for MCF-7 cells. In both cell lines, increased levels of Bax and caspase 3, along with downregulation of BCL-2 and positive annexin V staining, were observed, confirming apoptosis. Moreover, the colony-forming abilities in both cell lines decreased after C1 and C3 complex treatment. All these results suggest that the compounds C1 and C3 may have potential in the treatment of breast cancer, though further research is needed to confirm their efficacy.

Direct embryonic biopsy with transcervical embryoscopy is an effective method for karyotyping and morphology assessment in miscarriages.

PURPOSE: The main purpose of this study is to compare the validity of transcervical embryoscopy method with standard uterine evacuation method in detecting more accurate karyotypes in miscarriages below tenth week of pregnancy. Additionally, the frequency and distribution of fetal morphological abnormality were evaluated. METHODS: A prospective study was carried out at the Gazi University Faculty of Medicine, Department of Obstetrics and Gynecology. Patients with missed abortions between sixth and tenth gestational weeks were included in the study group, and fetal morphological examination and direct embryonic biopsy were performed by transcervical embryoscopy. The control group consisted of patients who experienced miscarriage and genetic material obtained from routine uterine evacuation between February and October 2023. RESULT: A total of 60 patients in the study group and 189 patients in the control group were evaluated. The median ages, previous miscarriage numbers, median gravida numbers, and median gestational weeks were comparable between groups. Chromosomal abnormality was detected in 24 (42.8%) and 52 embryos (29.9%) in the study and control groups, respectively (p = 0.004). Culture failure rates were 6.6% (n = 4) and 7.9% (n = 15) in the study and control groups, respectively. In the study group, 12 embryos had a morphological abnormality in which 6 of them had normal karyotype. CONCLUSION: Direct embryonic biopsy with transcervical embryoscopy is an effective method to exclude maternal decidual cell contamination and placental mosaicism in miscarriages for karyotype analysis. In addition, detecting anomalies in morphology might contribute our understanding in the process of miscarriages which arises independent from structural/numerical chromosomal abnormalities.

Use of serum copper and zinc levels in the diagnostic evaluation of endometrioma and epithelial ovarian carcinoma.

OBJECTIVE: The aim of this study is to evaluate serum copper (Cu) and zinc (Zn) levels in patients with epithelial ovarian cancer and endometrioma. MATERIALS AND METHODS: We included 21 epithelial ovarian cancer patients, 47 endometrioma patients, 31 healthy women of reproductive age, and 10 healthy women in menopause. Cu and Zn levels and Cu/Zn ratios were compared. RESULTS: In the endometrioma group, Cu levels (P = 0.04) and Cu/Zn ratio (P < 0.01) were higher, while Zn levels (P < 0.01) were lower compared to the control group. The threshold value of 1.15 with 62% sensitivity and 61% specificity was calculated for the Cu/Zn ratio using the ROC curve (AUC = 0.688; P = 0.005). In the ovarian cancer group, Cu levels (P ≤ 0.01) and Cu/Zn ratio (P = 0.02) were higher, whereas Zn levels (P ≤ 0.02) were lower compared to the control group. The Cu/Zn ratio threshold value of 1.37 was calculated with 76% sensitivity and 90% specificity (AUC = 0.829; P = 0.004). The Zn level was lower (P = 0.02), and the Cu/Zn ratio was higher (P = 0.01) in the ovarian cancer group compared to the endometrioma group. CONCLUSION: The threshold value of the Cu/Zn ratio for ovarian cancer could be determined with a specificity of 90%, whereas the sensitivity and specificity of the Cu/Zn ratio for endometrioma were low.

Dual trigger with the combination of gonadotropin-releasing hormone agonist and standard dose of human chorionic gonadotropin improves in vitro fertilisation outcomes in poor ovarian responders.

The study aimed to evaluate the impact of the dual trigger with the combination of GnRH agonist and standard dose of recombinant hCG on IVF outcomes in poor ovarian responders with GnRH antagonist protocol. 1283 cycles of 1010 poor responder patients according to Bologna criteria were retrospectively analysed in terms of final oocyte maturation: dual trigger group (250 µg hCG + 0.2 mg triptorelin) or standard group (250 µg hCG). Primary outcome measures were the number of retrieved and mature oocytes. The secondary outcome measures were clinical pregnancy rates and live birth rates.The number of retrieved oocytes, mature oocytes, and the top-quality embryos transferred were significantly higher in the dual trigger group (p < .001). Fertilisation rates (73.6% vs 69.6%, p = .009), implantation rates (18.7% vs 14.6, p = .039), clinical pregnancy rate per embryo transfer (27.5% vs. 19.9%, p = .010) and live birth rate per embryo transfer (21.6% vs. 14.9%, p = .011) were also significantly higher in the dual trigger group as compared to the hCG trigger group. The usage of dual trigger with a GnRH agonist and a standard dosage of hCG could improve clinical pregnancy rates and live birth rates in poor ovarian responders undergoing GnRH antagonist IVF/ICSI cycles.IMPACT STATEMENTWhat is already known on this subject? Dual trigger with standard dose of hCG has been the subject of trials in normal responders to optimise IVF outcomes. The results of these studies showed significant improvements in implantation and pregnancy rates with an increase in the number of mature oocytes retrieved. As a result, dual trigger has become a popular ovulation trigger option in GnRH antagonist cycles.What do the results of this study add? There is limited data about the use of dual trigger in poor ovarian responders (PORs). According to our study, increasing the number of retrieved oocytes, mature oocytes, the number of fertilised oocytes, the number of transferred embryos and top quality embryos transferred by using dual trigger in patients with PORs have a positive impact on pregnancy outcomes.What are the implications of these findings for clinical practice and/or further research? These findings implies potential advantages of dual trigger usage for improving IVF outcomes in PORs. With large sample sized prospective randomised trials, dual trigger with combination of GnRHa and a standard dose of hCG might replace the traditional ovulation trigger with hCG in PORs.

Subsequent IVF outcomes following antibiotic therapy for chronic endometritis in patients with recurrent implantation failure.

AIM: The aim is to identify the chronic endometritis (CE) incidence in recurrent implantation failure (RIF) patients undergoing in vitro fertilization (IVF) treatment and compare the IVF outcomes of RIF patients with CE following antibiotic therapy with RIF patients without CE. Another purpose is to compare the IVF outcomes of described RIF patients with patients undergoing the first cycle of IVF. METHODS: In this retrospective cohort study, CE was diagnosed with CD-138 immunohistochemical staining. Among RIF patients, two groups were formed as group 1, including patients diagnosed with CE and treated by antibiotics (n = 129), and group 2, including patients without CE (n = 103). Patients with the first IVF cycle having similar infertility etiologies with RIF patients were reviewed as group 3 (n = 932). RESULTS: CE was diagnosed in 55.6% of RIF patients. The number of oocytes retrieved was not different between groups. Implantation rates (IR) were similar after antibiotic treatment in RIF patients with or without CE. However, Group 3 had a higher IR (41.1%) than group 1 and 2 (23.1% and 30.1%, respectively) (p < 0.001). Clinical pregnancy (CPR) and live birth rates (LBR) were comparable between RIF groups. However, CPR and LBR were significantly higher in group 3 (48.6% and 40.5%) than group 1 (36.4% and 27.9%), and group 2 (37.9% and 30.1%) (p = 0.007 and p = 0.005, respectively). CONCLUSION: Unidentified endometrial factors except CE may also affect the implantation process, although CE is a frequent finding in patients with RIF. Reproductive outcomes may not be improved only with antibiotics in RIF patients with CE.

Comparison of frozen-thawed embryo transfer protocols in patients with previous cycle cancellation due to uterine peristalsis: a pilot study

Background/aim: To investigate the optimal protocol for frozen-thawed embryo transfer (FET) cycles in patients who previously had a cycle cancellation due to uterine peristalsis (UP). Materials and methods: Thirty-four patients with previous embryo transfer (ET) cancellation due to UP during artificial cycle (AC) were included retrospectively. In the proceeding cycle, endometrium was prepared with AC (n: 23) in AC-FET group or with stimulated cycle that contains letrozole (L) (n: 11) in L-FET group. Intravenous bolus dose of 6.75 mg atosiban (Tractocile; Ferring Pharmaceuticals, Switzerland) injection was performed to all patients of AC-FET group due to UP ≥ 4/min on the planned ET day of proceeding cycle. Atosiban was not used in L-FET group. Primary outcome was live birth rate (LBR) per ET. Secondary outcomes were clinical pregnancy rate (CPR) per ET, implantation rate (IR), cycle cancellation rate. Results: The baseline characteristics such as age, body mass index, antral follicle count, duration of infertility, and the number of prior in vitro fertilization attempts of each group were similar. The IR, CPR per ET, LBR per ET, CPR per cycle and LBR per cycle were significantly higher; cycle cancellation rates were significantly lower in L-FET group as compared to the AC-FET group. Conclusion: Endometrial preparation with letrozole significantly improves CPR and LBR in FET cycles of patients with previous cycle cancellations due to UP.

Advances in Controlled Oxygen Generating Biomaterials for Tissue Engineering and Regenerative Therapy.

Oxygen (O2) generating biomaterials are emerging as important compositions to improve our capabilities in supporting tissue engineering and regenerative therapeutics. Several in vitro studies demonstrated the usefulness of O2 releasing biomaterials in enhancing cell survival and differentiation. However, more efforts are needed to develop materials that can provide sustained O2 release for the long-term. In this paper, we present different O2 generating sources, including hydrogen peroxide, sodium percarbonate, calcium peroxide and magnesium peroxide, and also cover types of carriers and relevant methods of fabricating O2 generating systems. Then, the applications of O2 generating materials in supporting engineered constructs, supplying high O2 demanding cell transplants, and supporting ischemic tissues are discussed. Moreover, the challenges and future perspectives are highlighted.

Impact of the sexual abstinence period on the production of seminal reactive oxygen species in patients undergoing intrauterine insemination: A randomized trial.

AIM: To evaluate whether the duration of sexual abstinence has impact on oxidative stress in semen samples. METHODS: Oxidative reaction was tested for different levels of reactive oxygen species (ROS) by nitro blue tetrazolium assay in 90 patients with the diagnosis of unexplained or male factor infertility that were grouped into 3 groups as 0-2 (group 1), 3-4 (group 2) and >4 days (group 3) of duration of sexual abstinence. Subsequently, the remaining semen was prepared by gradient method for ovarian stimulation and intrauterine insemination (IUI) cycles to compare pregnancy rates in terms of different levels of ROS and different abstinence periods. RESULTS: Increased staining pigment intensity was related to higher level of ROS in >4 days' group as compared to groups 0-2 and 3-4 days (70% vs 43.3% and 50%, P = 0.013 and P = 0.014, respectively). Pregnancy rates significantly decrease with prolonged abstinence period (26.7%, 16.7% and 6.7% in groups 1, 2 and 3, respectively, P = 0.039). Progressive motile sperm count after gradient method of sperm preparation for IUI was highest in 3-4 days of abstinence period than shorter and longer abstinence groups. CONCLUSION: Longer duration of sexual abstinence causes higher oxidative stress and decreases pregnancy rates in IUI cycles.

Prisoners seeking healthcare in emergency department.

OBJECTIVE: To evaluate inmate referrals to emergency department of a tertiary healthcare facility in terms of demographical and clinical characteristics as well as their impact on the department. METHODS: The retrospective cross-sectional study was conducted at Ankara Numune Training and Research Hospital, Ankara, Turkey and comprised data of incarcerated patients who were brought to the emergency department from January 01, 2010, to December 31, 2012. Demographical characteristics, consultations, duration of hospitalisation, recurrent admissions, disposal and mortality rates were noted. The referrals were grouped as surgical conditions, medical disorders, Eye, Ear, Nose, Throat problems, injury and psychiatric disorders. The groups were then subdivided according to diagnosis. SPSS 22 was used for data analysis. RESULTS: Of the 856 patients, 804(93.4%) were men and 52(6.1%) were women. The overall mean age was 37.54±14.81 years (range: 15-83 years). The number of patients was the highest in the medical group 363(42.4%) and the lowest in the Eye, Ear, Nose, Throat group 56(6.5%). Mean age of the surgical group was significantly lower than the medical group (p<0.001) but significantly higher than that of the trauma group (p=0.001). CONCLUSIONS: Functional emergency response units, strict emergency triage of inmates and their rapid care and management in jails can help avoid referring these patients to already overcrowded emergency departments.